[The development of vaccination policy]. / Élaboration de la politique vaccinale.

THE DEVELOPMENT OF VACCINATION POLICY: In France, the minister of health is responsible for vaccination policy. Its development is based on the expertise of a Technical Committee on Vaccinations, attached to the High Authority of Health (HAS). The Committee's main missions are to issue recommendations and propose updates to the vaccination calendar. Its composition guarantees multidisciplinary expertise by integrating professionals interested in vaccination who must not have any conflict of interest. A response to referrals, usually from the Directorate-General for Health, is made according to different procedures depending on whether it is proposed to introduce a new vaccination strategy, to determine the place of a vaccine in an existing strategy, or to respond to emergency referrals. The epidemiology of the relevant disease as well as the efficacy and tolerance of vaccines are the essential elements taken into consideration. The production of evidence-based recommendations requires a systematic review of the literature with gradation of the level of evidence. Medico-economic studies are required for the introduction of new vaccine strategies. The draft opinion prepared by a working group is discussed and voted in plenary session. The project can be submitted to public consultation before validation by the college of the HAS. Downstream of this are the Transparency Commission which decides on reimbursement and the Public Health Economic Evaluation Commission which gives an opinion on efficiency which serves as a basis for discussions on price. Links established between these three commissions of the HAS are intended to ensure policy coherence.

Survey of delivery of prophylactic immunoglobulins following exposure to a measles case.

In France, almost 23,000 cases of measles and 10 deaths have been reported between January 2008 and August 2012. French health authorities recommend delivery of human polyvalent immunoglobulins in the event of exposure to a measles case for some categories of unvaccinated persons (children under the age of 12 months, immunocompromised persons and pregnant women), within six days after exposure and following laboratory confirmation of the contact case. We carried out a postal survey among 368 French hospital pharmacies to evaluate the number of persons affected by this measure between 1 January 2010 and 31 August 2011, to describe the characteristics of these patients and to evaluate the application of the recommendations in terms of delay between exposure and immunoglobulin delivery, and confirmation of the contact case. The response rate to the survey was 73%. In total, 400 immunoglobulin deliveries were listed, most of them for children under the age of one year, and 84% of the 250 administrations with available information occurred within six days after exposure, as recommended. However, only 48% of the 209 treated contacts with available information were laboratory-confirmed when the immunoglobulins were delivered. This survey is the first evaluation of this recommendation since its introduction in 2005 and suggests that the recommendations may need to be updated.

A report on the large measles outbreak in Lyon, France, 2010 to 2011.

In 2010 and 2011, the city of Lyon, located in the Rhône-Alpes region (France), has experienced one of the highest incidences of measles in Europe. We describe a measles outbreak in the Lyon area, where cases were diagnosed at Lyon University hospitals (LUH) between 2010 and mid-2011. Data were collected from the mandatory notification system of the regional public health agency, and from the virology department of the LUH. All patients and healthcare workers who had contracted measles were included. Overall, 407 cases were diagnosed, with children of less than one year of age accounting for the highest proportion (n=129, 32%), followed by individuals between 17 and 29 years-old (n=126, 31%). Of the total cases, 72 (18%) had complications. The proportions of patients and healthcare workers who were not immune to measles were higher among those aged up to 30 years. Consequently, women of childbearing age constituted a specific population at high risk to contract measles and during this outbreak, 13 cases of measles, seven under 30 years-old, were identified among pregnant women. This study highlights the importance of being vaccinated with two doses of measles vaccine, the only measure which could prevent and allow elimination of the disease.

Pediatric neurological complications associated with the A(H1N1)pdm09 influenza infection.

BACKGROUND: Influenza-related neurological complications (INC) have been reported during seasonal flu in children. OBJECTIVES: To investigate the types, outcomes and incidence of INC occurring during the 2009 A(H1N1) pandemic, a retrospective analyze was conducted in the single French pediatric hospital of Lyon from October 2009 to February 2010. STUDY DESIGN: All children presenting with fever, influenza-like illness, respiratory distress or neurological symptoms were tested for influenza A(H1N1)pdm09 infection from respiratory specimens using real time RT-PCR. RESULTS: INC occurred in 14 A(H1N1)pdm09 positive children (7.7% of A(H1N1)pdm09 positive children admitted to hospital) with a median age of 5.1 years. Admission to the intensive care unit (ICU) was required for nine children (64.3%). Half of the children with INC had comorbidity and three had coinfection, both characteristics mainly found in children requiring the ICU. All children received oral oseltamivir treatment. Febrile seizures were observed in eight children, half of them having a chronic comorbidity (2 epilepsy, 1 nonketotic hyperglycinemia, 1 anoxic encephalopathy). Other INC, less commonly reported, included 2 cases of encephalitis, 1 encephalopathy, 1 basilar artery thrombosis, 1 myasthenic crisis and 1 coma. Eleven of the 14 children (78.6%) recovered, one had a minor disability, one child developed a locked-in syndrome and one died from complications of an acute necrotizing encephalopathy. DISCUSSION: INC can be observed even in children with no underlying disorder. It may lead to dramatic issue in a significant number of cases.

Pragmatic management of Panton-Valentine leukocidin-associated staphylococcal diseases.

Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus is associated with a broad spectrum of diseases, ranging from common uncomplicated soft tissue infections to severe diseases such as complicated soft tissue infections, extensive bone and joint infections, and necrotising pneumonia. Specialised management of infection based on the presence of PVL may not be required for mild infections, whereas it could be lifesaving in other settings. Moreover, most severe PVL diseases are recently identified entities and a 'gold standard' treatment from comparatives studies of different therapeutic options is lacking. Thus, recommendations are based on expert opinions, which are elaborated based on theory, in vitro data and analogies with other toxin-mediated diseases. In this review, we consider the potential need for specialised PVL-based management and, if required, which tools should be used to achieve optimal management.

[Varicella-associated purpura fulminans and deep vein thrombosis: a pediatric case report]. / Purpura fulminans post-varicelleux et thrombose veineuse : à propos d'un cas pédiatrique.

Purpura fulminans (PF) and deep vein thrombosis are rare complications secondary to chicken pox disease. The presence of antibodies reflects an ongoing immunological process and requires specialized management. The present study reports a 4-year-old boy with no medical history who presented with purpura on the legs 10 days after chicken pox eruption. Laboratory tests showed a disseminated intravascular coagulation associated with low plasma protein C and S activities, and the presence of anti-protein S antibodies. A replacement therapy with protein C infusions and fresh frozen plasma was prescribed. The patient also underwent regular sessions of hyperbaric oxygen followed by the surgery. Fourteen days after the beginning of the purpuric lesions, he presented deep vein thrombosis (DVT) of the lower limbs and was treated with unfractionated heparin. This case report illustrates the pathophysiology of DVT occurring in a patient with chicken pox disease (i.e., acquired protein C and S deficiencies and anti-protein S autoantibodies) and emphasizes the utility of thrombophilia testing in order to better adapt treatment.

Respiratory viruses in children admitted to hospital intensive care units: evaluating the CLART® Pneumovir DNA array.

Viruses play a significant part in children's respiratory infections, sometimes leading to hospitalization in cases of severe respiratory distress. The aim of this study was to investigate respiratory infections in children treated in a hospital intensive care unit (ICU). Assays were performed using the CLART® Pneumovir DNA array assay (Genomica, Coslada, Madrid, Spain), which makes it possible to detect 11 genus of respiratory viruses simultaneously. During the winter of 2008-2009, 73 respiratory specimens collected from 53 children under 2 years of age and admitted to an ICU were tested. At least one virus was detected in 78% (57/73) of the samples. The virological diagnosis was based on single infections in 65% (37/57) and on multiple infections in 35% (20/57) of cases. The array assay revealed respiratory syncytial virus (RSV) in 73.6% (42/57) of the samples and rhinovirus in 24.6% (14/57), either on their own or in co-infections. All viruses identified in single and multiple infections were tested, taking into account clinical features, risk factors, and severity criteria. Children with no risk factors presented more multiple infections, up to 42% of cases, than children with at least one risk factor. RSV seemed to induce severe symptoms by itself as no difference in intubation needs was observed when RSV was detected on its own or in co-infection. The CLART® Pneumovir DNA array was useful for examining severe viral respiratory infections, when other viruses than those detected by conventional methods could be involved, particularly in an ICU.

Spotlight on measles 2010: update on the ongoing measles outbreak in France, 2008-2010.

Since early 2008, France has been experiencing a measles outbreak with almost 5,000 notified cases as of 30 June 2010, including three measles-related deaths. The proportion of cases 20 years or older reached 38% during the first half of 2010. This situation is the consequence of insufficient vaccine coverage (90% at age 24 months in 2007) that led to the accumulation of susceptibles over the last years. It underlines the need for additional measures targeting susceptible children and young adults.

Pandemic A(H1N1)2009 influenza virus detection by real time RT-PCR: is viral quantification useful?

The emergence of the influenza A(H1N1) 2009 virus prompted the development of sensitive RT-PCR detection methods. Most are real time RT-PCRs which can provide viral quantification. In this manuscript, we describe a universal influenza A RT-PCR targeting the matrix (M) gene, combined with an RNaseP RT-PCR. These PCRs allow the detection of all influenza A virus subtypes, including A(H1N1)2009, together with a real-time assessment of the quality of the specimens tested. These PCR procedures were evaluated on 209 samples collected from paediatric patients. Viral loads determined through Ct values were corrected according to the RNaseP Ct value. The mean viral load in the collected samples was estimated to be 6.84 log RNA copies/mL. For poor quality samples (RNaseP Ct > 27), corrections resulted in +3 to +8 Ct values for the M gene RT-PCR. Corrected influenza Ct values were lower in late samples. No correlation was established between viral loads and clinical severity or duration of disease.This study shows that real time RT-PCR targeting the matrix gene is a reliable tool for quantification of type A influenza virus but emphasises the need for sample quality control assessment through cellular gene quantification for reliable estimation of the viral load. This method would be useful for disease management when repeated specimens are collected from an infected individual.

[Septic osteomyelitis of the hip after Fusobacterium necrophorum pharyngitis]. / Ostéoarthrite de la hanche dans les suites d'une angine àFusobacterium necrophorum.

CASE REPORT: We report the case of a patient presenting with Lemierre's syndrome with an initial atypical presentation due to a predominant hip localization. Despite the adapted antibiotic treatment and surgical drainage, the patient relapsed. The bone and joint biopsy samples were sterile but the presence of the Fusobacterium necrophorum was demonstrated by PCR. CONCLUSION: Lemierre's syndrome may have different clinical presentations, due to the localizations of septic emboli. Careful attention should be paid to common ENT infections with an unfavorable evolution despite antibiotics. PCR has become a very interesting tool to document bone and joints bacterial infections when cultures are negative.

[Adjunctive therapies (excluding corticosteroids). Site of initial management]. / Traitements adjuvants autres que la corticothérapie et lieu de la prise en charge initiale.

Bacterial meningitis is still a serious disease with a high risk of mortality and sequels. The progress in antibiotic treatment has not improved the prognosis. Thus, optimizing the initial care and the treatment of the most severe cases should improve the outcome. No study has compared the outcome according to the level of care at the admission site. There is evidence that the most severe cases should be managed by critical care units. It seems reasonable to recommend initial admission of common cases to units able to provide intensive care. Most people now agree that fluid restriction has not demonstrated its efficiency, furthermore it might have deleterious effects. However, a fluid overload should be avoided. Maintaining cerebral perfusion is a key issue in the treatment of bacterial meningitis and requires monitoring both arterial blood pressure and intracranial pressure. Intracranial pressure monitoring is probably useful to optimize the treatment of the most severe cases. The aggressive treatments of cerebral edema have not been evaluated but seem, in some limited series, able to improve some life threatening situations. The benefit of systematic glycerol administration needs confirmation. Seizures should be treated with the usual medications. However, drugs with potentially deleterious effects on hemodynamics should be avoided. There is no sufficient evidence to support the administration of a systematic prophylactic treatment. Fever should be treated when above 39.5 degrees C/40 degrees C and in the case of intracranial hypertension. There is no clinical study to explore the modifications of fever on bacterial growth or on inflammation as observed in some experimental studies.

[Immunization: process of elaborating guidelines and their evolution in France]. / Vaccinations: élaboration des recommandations et de leur évolution en France.

French guidelines for immunization are elaborated by a permanent advisory committee (Comité technique des vaccinations), which is part of the Public Health Council. This committee is composed of 20 experts from the different medical specialties involved in the immunization process, who are appointed for 3 years by the French Ministry of Health. Other members, without voting power, represent de different agencies, affiliated to the health minister, other ministers and different institutions. All members have to declare and update their potential conflicts of interests. The committee establishes official guidelines concerning topics submitted from the National Health Care Authorities, industrial firms awarded marketing approval for a new vaccine, or in the event of a modification concerning a previous registration. The advisory committee can also decide itself to establish official guidelines on a given topic. A submission usually leads to the creation of a specific working group assigned the task of preparing a report and an advice project. The project is proposed for committee vote and subsequently validated by the Commission for Transmissible Diseases of the Superior Public Health Authority (Haut Conseil de la santé publique). The committee guidelines stipulate whether the vaccine should be recommended or not, the target population (universal or limited to a selected population) and the immunization schedule. The committee's advice statement may also mention the need for a specific survey of the impact of the vaccination on epidemiology, as well as a broader survey related to its safety. Usually, when a vaccine is recommended, the Transparency Commission of the Haute Autorité de santé and the economic committee on drugs decide on its reimbursement by the public health care fund. The guidelines become part of the immunization schedule, which is updated annually and published in the Official Bulletin of the Minister of Health and in the Bulletin épidémiologique hebdomadaire.

Measles resurgence in France in 2008, a preliminary report.

Since the beginning of 2008, France is experiencing a resurgence of measles. It started in a religious traditionalist group with low coverage and secondarily spread to the general population. This situation is the consequence of the insufficient vaccine coverage (less than 90 % at 24 months of age) which had led to the accumulation of susceptibles over the last years. More than 550 cases have been notified in 2008, the vast majority being unvaccinated. One measles-related death has occurred early 2009. Efforts to enhance communication to the general public and the health professionals on measles vaccination and control measures around cases are ongoing.

[Active drug monitoring of adverse drug reactions in pediatric emergency department]. / Recueil systématique et actif des évènements indésirables médicamenteux chez les enfants admis aux urgences pédiatriques.

OBJECTIVES: The aim of this study was to systematically evaluate adverse drug reactions (ADRs) in children consulting at the pediatric emergency unit during a 6-month period. METHOD: The regional pharmacovigilance center (CRPV) and the department of clinical pharmacology prospectively and systematically recorded all potential ADRs among patients younger than 18 years of age in the pediatric emergency unit reported at the daily staff meetings. All cases were then screened and validated by the CRPV. For validated cases, preventability, seriousness, and off-label use were evaluated. RESULTS: During the study period, from 1 March to 1 September 2005, 90 children presented potential adverse drug events. ADRs were confirmed in 43 patients, 19 females and 24 males. Thirty-four patients (79%) were under the age of 5. According to the European definition, 14 patients (33%) had serious ADRs. One anaphylactic shock after amoxicillin injection; antimalarial prophylaxis misuse leading to convulsive status epilepticus, convulsion, and coma after hepatitis B and MMR vaccines were deemed life-threatening. Three ADRs were considered avoidable. Antibiotics and vaccines were the most common possible cause of ADRs (76%). Skin reactions (n=27), fever (n=8), and gastric disorders (n=5) were the most common clinical manifestations. CONCLUSIONS: Because ADRs were reported by clinicians on a voluntary basis, serious ADRs were probably reported more systematically. Compared to a similar period without active monitoring, active drug monitoring of ADRs doubled the number of confirmed cases 43 vs 17, p<0.001. Close collaboration between the pharmacovigilance center, pharmacologists, and clinicians is necessary and seems feasible for improving the monitoring of ADRs in children.

Role of Mycoplasma pneumoniae in pediatric encephalitis.

A retrospective study investigating all the infectious encephalitis cases hospitalized at the pediatric intensive care unit of Edouard Herriot University Hospital in Lyon, France, was carried out in order to estimate the prevalence of Mycoplasma pneumoniae in acute childhood encephalitis. From January 2001 to December 2005, the cases of 29 children were selected and reviewed. M. pneumoniae related encephalitis was considered as probable in five cases (17%) on the basis of positive serological tests or positive polymerase chain reaction (PCR) tests in throat or nasopharyngeal swab while the PCR tests performed from the cerebrospinal fluid were negative. This study suggests that M. pneumoniae may be a major cause of infectious encephalitis in children as well as enteroviruses or Epstein-Barr virus detected in five and three cases, respectively.

[Vaccination coverage among health care workers in the pediatric emergency and intensive care department of Edouard Herriot hospital in 2007, against influenza, pertussis, varicella, and measles]. / Couverture vaccinale du personnel hospitalier du service d'urgences et de réanimation pédiatriques de l'hôpital Edouard-Herriot de Lyon en 2007, concernant la grippe, la coqueluche, la varicelle et la rougeole.

AIM: The aim of this study was to determine the vaccination coverage among the medical and paramedical health care workers of the pediatric intensive care and emergency department of Edouard Herriot hospital in Lyon, with respect to influenza, pertussis, varicella, and measles, 4 diseases with air transmission and vaccination recommendations. METHOD: During February and March 2007, a questionnaire was given by hand to 123 health care workers by a medical student working there or available in the intensive care unit. RESULTS: The response rate to the questionnaire was 68.3%. The vaccination coverage against influenza was 42.8%; men and medical health care workers were better vaccinated. With respect to vaccination against pertussis, one third had received an injection in adulthood, adults under age 30 and medical health care workers were better vaccinated, but the difference was not statistically significant. Ten health care workers were not vaccinated and had no history of measles: only 1 had had a measles serology and none were vaccinated. Eleven had no history of varicella: 6 had had a varicella serology and none were vaccinated. CONCLUSIONS: Vaccination coverage against influenza is higher than what has been reported in the literature, possibly because of a mobile vaccination campaign against influenza made during winter 2006 in this pediatric department. Vaccination coverage against pertussis is encouraging and probably the consequence of an awareness of the gravity of the disease among infants. Individual information is necessary for health care workers on the nosocomial risk for influenza and pertussis in infants, and vaccination must be proposed. Serology against varicella and measles is compulsory for all health care workers with no history and no vaccination against these 2 diseases, to track and vaccinate the nonimmunized personnel. Occupational physicians have a very important role to play in meeting this goal.